Viruses, Volume 12, Issue 11 (November 2020) – 142 articles
Cover Story (view full-size image): HIV-1 cure strategy by means of proviral knock-out using CRISPR-Cas9 has been hampered by the emergence of viral resistance against the targeting guide RNA (gRNA). Rapid viral rebound was evident after Cas9-gRNA disruption, due to the non-homologous end-joining (NHEJ)-mediated mutations inside the targeted proviral regions (e.g., LTR) that are non-deleterious to the virus. Here, we propose concentrated gRNA attacks against the integral HIV-1 tat to deplete post-editing viral fitness and block mutational escape. Analogous to the combination strategy of antiretroviral therapy (ART), combination of multiple gRNAs represents a promising method to inhibit viral escape from CRISPR-Cas9, thus elevating the gene editing platform to achieve long-term HIV-1 cure. View this paper.
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